Cysteine Protease Bleomycin Hydrolase Genomic Structure and Genetic Mapping of the Human Neutral

نویسندگان

  • Susana E. Montoya
  • Robert E. Ferrell
  • John S. Lazo
چکیده

Bleomycin hydrolase (BH) is the only known eukaryotic enzyme that inactivates the widely used antineoplastic agent bleomycin (BLM) and is a primary candidate gene for protection against lethal BLM-induced pul monary fibrosis and for BLM resistance in tumors. Human B!! was found to exist as a single gene that was mapped to chromosome 17 using National Institute of General Medical Sciences human/rodent hybrid mapping panels and localized to 17q11.1—11.2 by linkage analysis using the Centre d'Etude du Polymorphisme Humain reference database. The human BH gene consisted of 11 exons ranging in size from 69—198 bp separated by introns ofapproximately 1kb, reflectingthe archetypal genomicstructure of the cysteine protease family. A polymorphic site was identified in the eleventh exon at bp 1450 encodIng either valine or Isoleucine. These fmdings provide essential tools requlred to define the role of RH in BLM-induced pulmonary fibrosis and BLM resistance in tumors.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Genomic structure and genetic mapping of the human neutral cysteine protease bleomycin hydrolase.

Bleomycin hydrolase (BH) is the only known eukaryotic enzyme that inactivates the widely used antineoplastic agent bleomycin (BLM) and is a primary candidate gene for protection against lethal BLM-induced pulmonary fibrosis and for BLM resistance in tumors. Human BH was found to exist as a single gene that was mapped to chromosome 17 using National Institute of General Medical Sciences human/ro...

متن کامل

BLH1 codes for a yeast thiol aminopeptidase, the equivalent of mammalian bleomycin hydrolase.

We have cloned the BLH1 gene of the yeast Saccharomyces cerevisiae coding for a peptidase with significant homology to rabbit bleomycin hydrolase. Bleomycin is a glycopeptide antibiotic used for the treatment of human cancers. The antitumor activity of the drug is limited by its metabolic inactivation caused by bleomycin hydrolase, a member of the cysteine protease family. The open reading fram...

متن کامل

The neutral cysteine protease bleomycin hydrolase is essential for epidermal integrity and bleomycin resistance.

The papain superfamily member bleomycin hydrolase (Blmh) is a neutral cysteine protease with structural similarity to a 20S proteasome. Bleomycin (BLM), a clinically used glycopeptide anticancer agent, is deaminated in vitro by Blmh. We used gene targeting to generate mice that lack Blmh and demonstrated that Blmh is the sole enzyme required for BLM deamination. Although some Blmh null mice wer...

متن کامل

Neutral cysteine protease bleomycin hydrolase is essential for the breakdown of deiminated filaggrin into amino acids.

Filaggrin is a component of the cornified cell envelope and the precursor of free amino acids acting as a natural moisturizing factor in the stratum corneum. Deimination is critical for the degradation of filaggrin into free amino acids. In this study, we tried to identify the enzyme(s) responsible for the cleavage of deiminated filaggrin in vitro. First, we investigated citrulline aminopeptida...

متن کامل

Cloning and expression analysis of human bleomycin hydrolase, a cysteine proteinase involved in chemotherapy resistance.

A cDNA encoding human bleomycin hydrolase, a member of the cysteine proteinase family of proteins, has been cloned from a human brain cDNA library. The isolated cDNA contains an open reading frame coding for a polypeptide of 456 amino acids that contains all of the structural features characteristic of cysteine proteinases, including the cysteine, histidine, and asparagine residues that are ess...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره   شماره 

صفحات  -

تاریخ انتشار 2006